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The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe infections profoundly alter host metabolism, prior studies have largely ignored microbial metabolism in this context. Here, we describe an iterative, comparative metabolomics pipeline to uncover microbial metabolic features in the complex setting of a host and apply it to investigate gram-negative bloodstream infection (BSI) in patients. We find elevated levels of bacterially derived acetylated polyamines during BSI and discover the enzyme responsible for their production (SpeG). Blocking SpeG activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity also enhances bacterial membrane permeability and increases intracellular antibiotic accumulation, allowing us to overcome AMR in culture and in vivo. This study highlights how tools to study pathogen metabolism in the natural context of infection can reveal and prioritize therapeutic strategies for addressing challenging infections.
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Metabolômica , Poliaminas , Humanos , Animais , Poliaminas/metabolismo , Camundongos , Bacteriemia/microbiologia , Bacteriemia/metabolismo , Bacteriemia/tratamento farmacológico , Antibacterianos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/metabolismo , FemininoRESUMO
Processing CO2 into value-added chemicals and fuels stands as one of the most crucial tasks in addressing the global challenge of the greenhouse effect. In this study, we focused on the complex (dpp-bian)NiBr2 (where dpp-bian is di-isopropylphenyl bis-iminoacenaphthene) as a precatalyst for the electrochemical reduction of CO2 into CH4 as the sole product. Cyclic voltammetry results indicate that the realization of a catalytically effective pattern requires the three-electron reduction of (dpp-bian)NiBr2. The chemically reduced complexes [K(THF)6]+[(dpp-bian)Ni(COD)]- and [K(THF)6]+[(dpp-bian)2Ni]- were synthesized and structurally characterized. Analyzing the data from the electron paramagnetic resonance study of the complexes in solutions, along with quantum-chemical calculations, reveals that the spin density is predominantly localized at their metal centers. The superposition of trajectory maps of the electron density gradient vector field ∇ ρ r ${\nabla \rho \left({\bf r}\right)}$ and the electrostatic force density field F e s r ${{{\bf F}}_{{\rm e}{\rm s}}\left({\bf r}\right)}$ per electron, as well as the atomic charges, discloses that, within the first coordination sphere, the interatomic charge transfer occurs from the metal atom to the ligand atoms and that the complex anions can thus be formally described by the general formulae (dpp-bian)2-Ni+(COD) and (dpp-bian)2 -Ni+. It was also shown that the reduced nickel complexes can be oxidized by formic acid; resulting from this reaction, the two-electron and two-proton addition product dpp-bian-2H is formed.
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The atomic precision of metal nanoclusters and variability of surface ligands pave the way for its rational design and functionalization, whereas the property strengthening in multiple ways has been long challenging. Herein, improved amphiphilicity, chirality, thermostability, and strong CPL (circularly polarized luminescence) properties have been accomplished by facile ligand exchange of [Au23(CHT)16]- with HCapt (HCHT and HCapt denote cyclohexanethiol and captopril). In addition, the obtained chiral [Au23(SR)16]- (short for [Au23(CHT)16-x(Capt)x]-) clusters show specific binding affinity to remote-diamines (such as arginine and single/double strand DNA), originating from the hydrogen bonding and Van der Walls interaction among the surface Capt ligands and the di-amine groups.
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A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.
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INTRODUCTION: This in vitro study aimed to evaluate the effect of three different chemical agents on stain removal and mineral uptake of artificial dentin caries (ADC) lesions treated with silver diamine fluoride (SDF). METHODS: Baseline L*a*b* values were determined in polished human permanent dentin blocks, and ADC lesions were induced with an acid gel for 1 week. Samples were assigned to four groups; in three groups, half of each sample received SDF (30% SDF for 3 min), while the other half received SDF followed by a bleaching treatment protocol (garlic extract, bentonite, or 35% hydrogen peroxide). The fourth group had one SDF-treated half and one half without SDF. Color changes (ΔE) were measured by spectrometry, and transversal microradiography was used to quantify integrated mineral loss (ΔZ) 24 h after treatment (SDF or SDF + bleaching). A two-way mixed ANOVA was applied to thirty percent. RESULTS: SDF application increased mineral uptake by ADC (p = 0.001). The type of chemical agent evaluated (p < 0.0001), time (p = 0.01), and their interaction (p < 0.0001) bleached the ADC treated with SDF. However, 35% hydrogen peroxide was the only compound with a bleaching effect (p < 0.001), without returning to baseline color. None of the compounds altered the mineral uptake effect of SDF (p = 0.30). CONCLUSION: This in vitro study showed mineral uptake effect in ACD within 24 h after SDF application and the ability of hydrogen peroxide to partially remove (reduction of 24%) the staining caused by SDF without affecting its mineral uptake effect.
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Corantes , Suscetibilidade à Cárie Dentária , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Peróxido de Hidrogênio/farmacologia , Minerais , Dentina/diagnóstico por imagem , Fluoretos TópicosRESUMO
Flexible polyurethane foams (PUF) are used in many consumer products. PUF may contain trace levels of aromatic diamine impurities that could represent a potential health risk. The risk associated with sleeping on a PUF mattress was evaluated. Toxicity benchmarks for sensitization and non-cancer endpoints were derived from the respective points-of-departure using standard assessment factors. For the cancer endpoints, toxicity benchmarks were derived from the 25th-percentile values of animal studies. Recently published emission and migration data allowed to link exposure with the CertiPURTM voluntary quality limits of ≤5 mg.kg-1 for 2,4-toluene diamine and 4,4'-methylene dianiline in PUF. Using conservative exposure scenarios, lifetime-average daily internal doses from the combined inhalation and dermal exposures were calculated. Margins of safety for non-cancer and sensitization endpoints were >104. The theoretical excess cancer risk was ≤1.5 × 10-7. It is concluded that sleeping on a mattress that satisfies the CertiPUR limit value does not pose undue risk to consumers.
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Diaminas , Poliuretanos , Animais , Medição de Risco , ToluenoRESUMO
This study aimed to evaluate the effect of dentin hypersensitivity treatments on immediate and long-term shear bond strength (SBS) of composite restorations. Ninety non-carious extracted human molars were cut to expose dentin, which was embedded in acrylic resin, and randomly divided into three groups (n = 30/group) according to surface treatment: 1) no treatment (C and C*; control); 2) silver diamine fluoride with potassium iodide (SDF/KI and SDF/KI*; Riva Star); and 3) nano-hydroxyapatite (nHAp and nHAp*; PrevDent). The specimens were etched through the etch-and-rinse technique, followed by universal adhesive application and resin composite cylinders (2.38 mm in diameter × 3.5 mm high). The SBS was tested immediately (24 h after the restoration) and after thermocycling (*) (5000 cycles, 5 °C to 55 °C) at a 0.5 mm/min crosshead speed using a universal testing machine. A stereomicroscope was used to evaluate the mode of failure, and representative scanning electron microscopy (SEM) images were also acquired. Data normality was verified, and two-way ANOVA and Tukey's post hoc tests were performed for multiple comparisons (α = 0.05). The control group presented the highest SBS (27.10 MPa), while SDF/KI* had the lowest values (6.87 MPa). nHAp-based desensitizer exhibited higher SBS than SDF/KI for both immediate (22.6 MPa) and thermocycled (19.03 MPa) conditions. No intragroup difference was evidenced between immediate and thermocycled samples for any group. Most specimens for the C and nHAp groups presented mixed failure, while the SDF/KI groups presented comparable adhesive and mixed failures. The SBS of adhesive restorations after the application of desensitizing agents is material dependent, where SDF/KI reduces SBS values below the acceptable minimum bond strength, while the nHAp application meets the minimally required bond strength.
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Colagem Dentária , Adesivos Dentinários , Humanos , Adesivos Dentinários/química , Colagem Dentária/métodos , Dentina , Pirenos , Teste de Materiais , Cimentos de Resina/química , Resistência ao CisalhamentoRESUMO
OBJECTIVE: This study aimed to assess the remineralization efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), silver diamine fluoride/potassium iodide (SDF/KI), and sodium fluoride with functionalized tricalcium phosphate (NaF/fTCP) on artificial early enamel lesion using laser fluorescence and micro-CT analysis. METHODOLOGY: On extracted impacted third molars, artificial enamel lesions were prepared. Twenty-eight specimens were randomly assigned to four groups (n = 7 per group): a control group (artificial saliva), CPP-ACP (GC Tooth Mousse), SDF/KI (Riva Star), and NaF/fTCP (Clinpro White varnish). Following the manufacturer's instructions, the remineralization agents were applied to demineralized surfaces. Laser fluorescence and micro-CT were used to evaluate the remineralization efficacy of the agents and analyzes were performed during four stages: before demineralization, after demineralization, 1st day of remineralization and 30th day of remineralization. Shapiro-Wilk test, repeated measures two-way ANOVA, and Spearman correlation tests were used for statistical analysis. A significant level of p < 0.05 was established. RESULTS: SDF/KI significantly reduced the lesion area and lesion volume on the demineralized enamel surface after 30 days of remineralization. In the T3 period, SDF/KI increased the mineral density statistically significantly compared to the T1 period. The laser fluorescence values for all three remineralizing agents exhibited a linear decrease. A significant correlation between the fluorescence values and the mineral density was found (p = 0.01). CONCLUSION: All three investigated agents were showed positive remineralization efficacy on artificial enamel lesion. However, SDF/KI, containing silver diamine fluoride and potassium iodide exhibited superior than other agents in promoting remineralization. CLINICAL SIGNIFICANCE: Although all three remineralization agents showed positive remineralization efficacy on artificial enamel lesions, SDF had higher remineralization performance over the other two agents. SDF has potential to prevent progression of demineralization in treating children with high caries risk in the long-term.
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The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A-D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L-1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L-1. As determined by structure-activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L-1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.
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Benzamidas , Fluorocarbonos , Inseticidas , Mariposas , Praguicidas , Animais , Estrutura Molecular , Diamida/química , Relação Estrutura-Atividade , Inseticidas/farmacologia , Inseticidas/química , SulfóxidosRESUMO
BACKGROUND: Parental perceptions of staining due to silver diamine fluoride (SDF) could affect its utilization in paediatric dentistry. This study represents the second part of a wider project focused on SDF esthetic acceptability among Italian parents. AIM: To evaluate parental acceptance of SDF staining in Italy and to assess whether the parent's level of acceptance depends on location, child's behavior, or demographic background. DESIGN: A cross-sectional study was conducted among Italian parents of children attending two university dental clinics. We used a validated Italian version of the questionnaire "Parental Perceptions of Silver Diamine Fluoride Dental Color Changes." RESULTS: Two hundred and thirty-four parents took part in the survey. Of parents, 65.4% considered the staining on posterior teeth esthetically "acceptable" or "somewhat acceptable," and 19.3% on anterior teeth (p = .001). In a scenario of positive cooperation, 48.5% of parents were "somewhat likely" or "very likely" to choose SDF to treat posterior teeth, and 17.6% on anterior teeth (p = .001). Level of acceptance increased as the difficulty the child would experience to receive conventional treatment increased. CONCLUSION: Staining on posterior teeth is more acceptable to parents than staining on anterior teeth. Level of acceptance on anterior teeth increases when sedation or general anesthesia is the alternative for the child.
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BACKGROUND: No studies have evaluated the unique potential of nurse-led silver diamine fluoride (SDF) application for children to bridge the gap in interprofessional collaboration. AIM: To investigate the attitudes, beliefs and perceptions of nurses regarding nurse-led SDF application at the well-child visit and identify possible barriers and make recommendations. DESIGN: Mixed methods design involving a questionnaire and semi-structured individual interviews were conducted. RESULTS: All eligible nurses (n = 110) completed the questionnaire, and 16 were interviewed. Questionnaire responses highlighted that nurses were not confident in providing oral health services (score: <3 of 5) beyond oral hygiene advice (score: ≥3.9 of 5) but believed that they should be providing these services for individuals with difficulty accessing care. Interviews reflected that most nurses viewed oral health care as an important part of paediatric health but were limited by knowledge, time and manpower. Most were willing to expand their job scope to include SDF application with formal education and training, competency assessments and approaches to counter time limitations. CONCLUSION: Where nurses are already providing basic oral healthcare, nurse-led SDF application could be the next step. Findings suggest that systemic changes should include strategies to empower and motivate nurses to apply SDF at the well-child visit.
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Atitude do Pessoal de Saúde , Fluoretos Tópicos , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Fluoretos Tópicos/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Inquéritos e Questionários , Feminino , Criança , Masculino , Adulto , Cariostáticos/uso terapêutico , Assistência Odontológica para Crianças/métodosRESUMO
In this paper, urethane-based acrylates (UA) were prepared via an environmentally friendly non-isocyanate route. Isophorone diamine (IPDA) reacted with ethylene carbonate (EC), producing carbamate containing amine and hydroxyl groups, which further reacted with neopentyl glycol diacrylate (NPGDA) by aza Michael addition, forming UA. The structures of the obtained intermediates and UA were characterized by 1H NMR and electrospray ionization high-resolution mass spectrometry (ESI-HRMS). The photopolymerization kinetics of UA were investigated by infrared spectroscopy. The composite with obtained UA can be UV cured quickly to form a transparent film with a tensile strength of 21 MPa and elongation at break of 16%. After UV curing, the mono-functional urethane acrylate was copolymerized into the cross-linked network in the form of side chains. The hydroxyl and carbamate bonds on the side chains have high mobility, which make them easy to form stronger dynamic hydrogen bonds during the tensile process, giving the material a higher tensile strength and elongation at break. Therefore, the hydrogen bonding model of a cross-linked network is proposed. The composite with UA can be 3D printed into models.
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BACKGROUND: This study aimed to evaluate the effect of Silver Diamine Fluoride (SDF) on the microleakage of flowable resin composite (FRC) and resin-modified glass ionomer cement (GIC) restorations bound to carious primary dentin. METHODS: Forty-four extracted carious primary molars were allocated into four groups as follows (n = 11 teeth/group): Group I, Flowable resin composite (FRCa): SDF38% treatment + FRC, Group II, Flowable resin composite (FRCb): FRC without SDF treatment, Group III, Resin-modified glass ionomer cement (GICa): SDF38% treatment + GIC, Group IV, Resin-modified glass ionomer cement (GICb): GIC without SDF treatment. Specimens were subjected to thermo cycling at 500 cycles between 5 to 55 °C (dwell time of 60 seconds) in baths before being immersed for 24 h in a 1% toluidine blue solution. Microleakage testing was conducted for each specimen in two areas; occlusal and gingival. Specimens were evaluated under stereomicroscope at 4x magnification. Results were analyzed using Kruskal-Wallis test followed by pairwise comparisons utilizing Dunn's post hoc test at p ≤ 0.05. RESULTS: Insignificant differences between different groups (p = 0.49) were observed at the gingival walls area readings. The highest value was found in GICb (2.33 ± 0.52), while the lowest value was found in FRCa (1.71 ± 0.76). Insignificant differences between different groups (p = 0.982) were observed at the occlusal walls area readings. The highest value was found in FRCa (1.43 ± 0.98), while the lowest value was found in GICb (1.17 ± 1.33). CONCLUSION: SDF does not adversely affect the microleakage of FRC and GIC restorations bound to carious primary dentin.
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Cárie Dentária , Cimentos de Ionômeros de Vidro , Compostos de Prata , Humanos , Cimentos de Ionômeros de Vidro/uso terapêutico , Restauração Dentária Permanente/métodos , Resinas Compostas/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Cárie Dentária/terapia , Dentina , Cimentos de Resina , Teste de Materiais , Fluoretos TópicosRESUMO
BACKGROUND: Using Silver Diamine Fluoride (SDF) may be an effective public health approach for managing dental caries in children. Parental acceptance of SDF has rarely been investigated in low-income and middle-income countries (LMICs). The aim of this study was to evaluate parental acceptance of SDF to manage dental caries in children aged 2-12 in Iran and Tajikistan. METHODS: This cross-sectional study was conducted in the Kurdistan province of Iran and Khatlon region of Tajikistan, 2022-2023. Parents watched a video about SDF and its weaknesses and strengths as compared to conventional approaches before completing the questionnaire. We also reported Prevalence Ratios with 95% confidence intervals for the relationship between parental acceptance and associated demographic factors as well as dental attitude and experience. RESULTS: Participants were 245 and 160 parents in Iran and Tajikistan, respectively. In both countries, a majority (Iran: 61.6%, Tajikistan: 77.9%) accepted SDF over conventional treatments for all primary teeth. The majority also accepted SDF only for posterior permanent teeth (Iran: 73.5%, Tajikistan: 78.7%). Black discoloration was the main reason for rejecting SDF. Overall, demographic factors and dental experience and attitude were not significantly associated with SDF acceptance. CONCLUSIONS: SDF was widely accepted by Iranian and Tajik parents. Establishing parental acceptance of SDF is an important step toward its application in LMICs where inexpensive solutions are needed.
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Cariostáticos , Fluoretos Tópicos , Pais , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Estudos Transversais , Fluoretos Tópicos/uso terapêutico , Criança , Pais/psicologia , Feminino , Masculino , Irã (Geográfico) , Tadjiquistão , Pré-Escolar , Compostos de Amônio Quaternário/uso terapêutico , Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Adulto , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
BACKGROUND: The black staining effect of silver-containing solutions for use to arrest caries can have a negative aesthetic impact on children and parents. This study aims to assess the staining effects of Silver Diamine Fluoride/Potassium Iodide (SDF/KI), SDF and Nanosilver Fluoride (NSF). MATERIALS AND METHODS: Forty-four extracted carious primary molars were collected and randomly divided into four groups (n = 11). The carious tissue in all teeth was removed using a chemo-mechanical caries removal agent with an excavator. After caries removal in all groups, SDF, SDF/KI, and NSF were applied to the different groups, while no solution was applied to the control group. Subsequently, the teeth in all groups were restored with compomer. Color values L*, a* and b* were measured using a spectrophotometer at three time points: immediately after compomer restoration (T0), one week later (T1), and four week later (T2). Changes in brightness (ΔL) and color (ΔE) over time were calculated and comparisons among groups were made. RESULTS: The SDF solution induced statistically significant black staining (p = 0.013) and a decrease in L* value (p < 0.001) on the compomer material compared to the other groups over time. CONCLUSIONS: It was observed that SDF/KI has the potential to reduce the black staining effect of SDF, though not entirely. Novel experimental solutions like NSF may offer an alternative to counteract the staining effect of SDF.
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Fluoretos Tópicos , Iodeto de Potássio , Compostos de Amônio Quaternário , Compostos de Prata , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Iodeto de Potássio/uso terapêutico , Humanos , Fluoretos Tópicos/uso terapêutico , Técnicas In Vitro , Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Descoloração de Dente/induzido quimicamente , Dente Decíduo , Espectrofotometria , Dente MolarRESUMO
BACKGROUND: The desirable properties of silver diamine fluoride (SDF) make it an effective agent for managing dental caries and tooth hypersensitivity. There are several clinical instances that SDF application might precede the placement of direct tooth-colored restorations. On the other hand, SDF stains demineralized/carious dental tissues black, which might affect the esthetic outcomes of such restorations. Color is a key parameter of esthetics in dentistry. Therefore, this study aims to systematically review dental literature on color/color change of tooth-colored restorations placed following the application of SDF on dentine. METHODS: Comprehensive search of PubMed, Embase, Scopus and ISI Web of Science databases (until August 2023) as well as reference lists of retrieved studies was performed. In vitro studies reported color or color change of tooth-colored restorative materials applied on SDF-treated dentine were included. Methodological quality assessment was performed using RoBDEMAT tool. Pooled weighted mean difference (WMD) and 95% confidence interval (95% CI) was calculated. RESULTS: Eleven studies/reports with a total of 394 tooth-colored restorations placed following a) no SDF (control) or b) SDF with/without potassium iodide (KI)/glutathione dentine pre-treatments were included. Color change was quantified using ∆E formulas in most reports. The pooled findings for the comparison of resin-based composite (RBC) restorations with and without prior 38% SDF + KI application revealed no statistically significant differences in ∆E values at short- and long-term evaluations (~ 14 days: WMD: -0.56, 95% CI: -2.09 to 0.96; I2: 89.6%, and ~ 60 days: WMD: 0.11; 95% CI: -1.51 to 1.72; I2: 76.9%). No studies provided sufficient information for all the items in the risk of bias tool (moderate to low quality). CONCLUSIONS: The limited evidence suggested comparable color changes of RBC restorations with and without 38% SDF + KI pre-treatment up to 60 days. The included studies lacked uniformity in methodology and reported outcomes. Further studies are imperative to draw more definite conclusions. PROTOCOL REGISTRATION: The protocol of this systematic review was registered in PROSPERO database under number CRD42023485083.
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Cor , Restauração Dentária Permanente , Dentina , Fluoretos Tópicos , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Dentina/efeitos dos fármacos , Restauração Dentária Permanente/métodosRESUMO
BACKGROUND: One of the most prevalent health problems affecting children worldwide is untreated caries in primary teeth. Agents to arrest caries are used to manage untreated decay in children in disadvantaged communities. Nano Silver Fluoride (NSF) overcomes the staining problems of Silver Diamine Fluoride (SDF). This study compared the clinical cariostatic effect of NSF to 38% SDF for arresting caries lesions. METHODS: The study included 360 children younger than 4 years, with at least one active lesion, ICDAS score ≥ 3, recruited from nurseries in a rural area in Alexandria, Egypt, in 2022. They were randomly assigned to receive a single application of NSF at baseline, or two applications of SDF at baseline and after 6 months. The arrest of active carious lesions was assessed after 6 and 12 months using ICDAS criteria, and parents' satisfaction with child appearance was also assessed. Chi-Square test was used to compare the groups and multi-level multiple logistic regression was used to assess the effect of the intervention on caries arrest at lesion level and binary logistic regression was used to assess the effect at patient level. RESULTS: 1853 active lesions were included in children whose mean (SD) age was 42.3 (8.2) months. The arrest rate was significantly higher in the NSF than the SDF group at lesion level (78.4% and 65.0% at 6 months and 71.3% and 56.3% at 12 months, p < 0.001). In regression analysis, NSF had significantly higher odds of caries arrest than SDF at lesion level (at 6 months, AOR = 2.57, 95% CI: 1.55, 4.26 and at 12 month, AOR = 3.27, 95% CI: 1.89, 5.67). Parents of children receiving NSF had significantly greater satisfaction with their children's dental appearance than those receiving SDF: (97.2% and 76.1%, respectively, p < 0.001). CONCLUSION: NSF demonstrated greater effectiveness in arresting caries in preschool children without inducing black staining of teeth and with greater parental satisfaction than SDF. NSF can be an alternative to SDF in arresting caries especially in underprivileged communities. TRIAL REGISTRATION: The trial was registered in the clinicaltrials.gov registry (#NCT05255913)-16/02/2022.
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Cariostáticos , Cárie Dentária , Fluoretos Tópicos , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Cárie Dentária/prevenção & controle , Compostos de Prata/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Pré-Escolar , Feminino , Masculino , Cariostáticos/uso terapêutico , Fluoretos/uso terapêutico , Lactente , Resultado do TratamentoRESUMO
We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation - spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength.
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Amina Oxidase (contendo Cobre) , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Animais , Ratos , Oxirredução/efeitos dos fármacos , Desaminação , Amina Oxidase (contendo Cobre)/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Poliamina Oxidase , Putrescina/metabolismo , Putrescina/farmacologia , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Sistema Livre de Células , Fígado/metabolismo , Fígado/efeitos dos fármacos , Poliaminas/metabolismo , Espermina/metabolismo , Espermina/farmacologia , Espermidina/metabolismo , Masculino , Nitrogênio/metabolismo , Ratos WistarRESUMO
A straightforward synthesis approach to chiral 1-aryl-2-aminoethanols via the one-pot asymmetric hydrogenation catalyzed by Ir catalyst was developed. This tandem process involves the inâ situ generation of α-amino ketones via the nucleophilic substitution of α-bromoketones with amines and the Ir-catalyzed asymmetric hydrogenation of ketone intermediates to provide diverse enantiomerically enriched ß-amino alcohols. The excellent yields and enantioselectivities (up to 96 % yield and up to >99 % ee) with a wide substrate scope in this one-pot strategy were obtained.
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Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase. The exposure of P19 neurons to histamine reduced cell viability to 65% maximally. This effect involves specific histamine receptors, since it was prevented by treatment with desloratadine and cimetidine, respectively, H1 and H2 antagonists, but not by the H3 antagonist ciproxifan. RT-PCR analysis showed that P19 neurons express H1 and H2 receptors, and the H3 receptor, although it seemed not involved in the histamine effect on these cells. The H4 receptor was not expressed. H1 and H2 antagonists as well as vegetal diamine oxidase diminished the intracellular Ca2+ mobilization triggered by histamine. The treatment with vegetal diamine oxidase or catalase protected against mortality and a significant reduction of H2O2 level, generated from the cells under the histamine action, was found upon treatments with desloratadine, cimetidine, vegetal diamine oxidase, or catalase. Overall, the results indicate the expression of functional histamine receptors and open the possibility of using P19 neurons as model system to study the roles of histamine and related drugs in neuronal pathogenesis. This model is less expensive to operate and can be easily implemented by current laboratories of analysis and by Contract Research Organizations.